Abstract: The invention provides a method of treating a disease or pathological condition resulting in apoptotic cell death. The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. Also provided is a method of prolonging the in vivo survival of transplanted cells for the treatment of a disease or pathological condition. The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells.

Abstract: The present invention relates to an isolated cyclic peptide, theta defensin, having antimicrobial activity, and to theta defensin analogs. A theta defensin can have the amino acid sequence Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa1-Xaa6-Xaa4-Xaa4-Xaa1-Xaa1-Xaa6-Xaa4-Xaa5-Xaa1-Xaa3-Xaa7-Xaa5, wherein Xaa1 to Xaa8 are defined; wherein Xaa1 can be linked through a peptide bond to Xaa8; and wherein crosslinks can be formed between Xaa3 and Xaa3, between Xaa5 and Xaa5, and between Xaa7 and Xaa7. For example, the invention provides a theta defensin having the amino acid sequence Gly-Phe-Cys-Arg-Cys-Leu-Cys-Arg-Arg-Gly-Val-Cys-Arg-Cys-Ile-Cys-Thr-Arg (SEQ ID NO:1), wherein the Gly at position 1 (Gly-1) is linked through a peptide bond to Arg-18, and wherein disulfide bonds are present between Cys-3 and Cys-16, between Cys-5 and Cys-14, and between Cys-7 and Cys-12. The invention also relates to antibodies that specifically bind a theta defensin and to isolated nucleic acid molecules encoding a theta defensin.

Abstract: The invention provides a transgenic non-human mammal comprising nucleated cells containing a transgene encoding an ataxin-2 polypeptide comprising a polyglutamine tract. In particular, the transgenic-non-human mammal can be a mouse. The invention also provides methods of using a transgenic non-human mammal expressing SCA2 encoding an ataxin-2 polypeptide to identify a therapeutic agent for use in treating a neurodegenerative disease by administering a compound to a transgenic non-human mammal expressing SCA2 encoding an ataxin-2 polypeptide and screening the transgenic non-human mammal for an improved neurological response associated with a neurodegenerative phenotype of the transgenic non-human mammal, thereby identifying a therapeutic agent for use in treating the neurodegenerative disease.

Abstract: The present invention relates to methods of preventing or reducing scarring in a wound area by administering decorin or biglycan to the wound.

Abstract: The present invention provides a method of identifying a tumor homing molecule that homes to angiogenic vasculature by contacting a substantially purified NGR receptor with one or more molecules and determining specific binding of a molecule to the NGR receptor, where the presence of specific binding identifies the molecule as a tumor homing molecule that homes to angiogenic vasculature. The invention also provides a method of directing a moiety to angiogenic vasculature in a subject by administering to the subject a conjugate including a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. In addition, the invention provides a method of imaging the angiogenic vasculature of a tumor in a subject by administering to the subject a conjugate having a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor and detecting the conjugate.

Abstract: The present invention is directed to a process for the production of a peptide, polypeptide, or protein having a predetermined property. In accordance with one embodiment, the process begins by producing by way of synthetic polynucleotide coupling, stochastically generated polynucleotide sequences. A library of expression vectors containing such stochastically generated polynucleotide sequences is formed. Next, host cells containing the vectors are cultured so as to produce peptides, polypeptides, or proteins encoded by the stochastically generated polynucleotide sequences. Screening or selection is carried out on such host cells to identify a peptide, polypeptide, or protein produced by the host cells which has the predetermined property. The stochastically generated polynucleotide sequence which encodes the identified peptide, polypeptide, or protein is then isolated and used to produce the peptide, polypeptide, or protein having the predetermined property.

Abstract: The present invention provides a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain. Non-antibody immunomodulatory molecules useful in the invention include immunostimulatory and immunosuppressive molecules such as cytokines. In one embodiment, the invention provides a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain and, additionally, a disease-associated antigen or immunogenic epitope thereof. Further provided by the invention are methods of modulating an immune response against a disease-associated antigen by administering to an individual a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain.

Abstract: The invention provides a method of inhibiting angiogenesis and treating pathologies with angioproliferative components. The invention provides a method of ameliorating tumor growth and metastasis in a subject comprising administering a superfibronectin or a superfibronectin-generating compound to the subject. The invention also provides a method of inhibiting the migration and attachment of tumor cells.

Abstract: The present invention provides mammalian retinoblastoma (Rb) protein-interacting zinc finger (RIZ) proteins, nucleic acid molecules encoding the RIZ and antibodies specific for the RIZ. The invention also provides screening assays for identifying an agent that effectively alters the association of a RIZ with a second molecule, which can bind to the RIZ. The invention also provides active fragments of RIZ containing the PR domain, which can regulate transcription. In addition, the invention provides methods for introducing a nucleic acid molecule-encoding a RIZ into a cell and for A-contacting a cell with an effective agent in order to modulate a function of a cell. Such methods are useful, for example, for inducing growth of a cardiac cell or a neuronal cell in a subject and for effecting normal growth control to a tumor cell or causing differentiation of tumor cells. The invention further provides methods for detecting a RIZ in a sample by detecting the RIZ or a nucleic acid molecule encoding the RIZ.

Abstract: The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. The vaccine is administered to the mammal in a manner that induces an immunologically effective response so as to affect the course of the disease. The invention additionally provides specific &bgr;-chain variable regions of the T cell receptor, designated V&bgr;6.2/3, V&bgr;6.5, V&bgr;2, V&bgr;5.1, V&bgr;13 and V&bgr;7, which are central to the pathogenesis of multiple sclerosis (MS).

Abstract: A method for producing human dendritic cells for therapeutic purposes which allows culture-deriving dendritic cells using no cytokines, or reduced cytokines. The method involves culturing mononuclear cells from blood or bone marrow in a medium containing at least one agent such as a calcium ionophore, e.g. A23187, theophylline, protaglandin E1, dibutyryl cyclic AMP, Vitamin D3, Vitamin E, retinoic acid, or a fatty acid. The culture is maintained for a sufficient time, typically 4-14 days, to produce a culture enriched for dendritic cells, as evidenced by at least about 2.5% of total cells exhibiting dendritic cell processes, or a dendritic dell antigen such as CD80, CD86, or CD1a. Also provided is a method to produce antigen-specific human T-cells by pulsing the dendritic cells obtained by the method of the invention with an antigen such as a viral, tumor, bacterial, or cell surface antigen, and then co-culturing T-cells with the antigen-pulsed dendritic cells.

Abstract: In accordance with the present invention, there are provided peptides that bind to a member of the mammalian selectin family and inhibit the binding of a carbohydrate to the selectin. Invention peptides are useful to inhibit of the adhesion of cells containing particular cell-surface carbohydrates to cells containing cell-surface selecting. Also provided are pharmaceutical compositions comprising invention peptides useful in methods for inhibiting a carbohydrate from binding to a selectin, and in methods of inhibiting tumor cell metastasis in a subject.

Abstract: The invention provides a method of preventing or reducing the severity of a cancer in a subject by stimulating the subject's immune response against the cancer. The invention provides, for example, a method of stimulating an immune response in a subject by administering to the subject tumor cells that are substantially similar to the subject's cancer cells and that are genetically modified to reduce or inhibit the expression of one or more immunosuppressive agents. The invention also provides a method of preventing or reducing the severity of cancer in a subject by stimulating the subject's immune response against the cancer by administering to the subject tumor cells that are substantially similar to the subject's cancer cells and that are genetically modified to prevent the expression of an immunosuppressive agents and, in combination with the genetically modified tumor cells, an immunostimulatory agent.

Abstract: The present invention relates to crosslink-stabilized analogs of indolicidin, which is a naturally occurring peptide having the amino acid sequence Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-CONH2 (“Indol 1-13;” SEQ ID NO: 1). The crosslinked indolicidin (“X-indolicidin”) analogs of the invention include, for example, analogs such as Indol 1-13(W6,9), which has the structure Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-CONH2 (SEQ ID NO: 3), and Indol 1-13/6,9C(C6,9), which has the structure Ile-Leu-Pro-Trp-Lys-Cys-Pro-Trp-Cys-Pro-Trp-Arg-Arg-CONH2 (SEQ ID NO: 4), where a crosslink formed between the first and last underlined amino acid residues. In addition, the invention provides nucleic acid molecules encoding the X-indolicidin analogs of the invention, particularly precursors of such analogs.

Abstract: The present invention provides methods of treating pathologies using Decorin.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: The present invention relates to microdroplets of a solution comprising a solvent having a boiling point of 150° C. or above, a surface tension of 30 dynes/cm or above, and a viscosity of 0.015 g/(cm)(sec). Such microdroplets are useful for the synthesis of chemical species, particularly biopolymers such as oligonucleotides and peptides, as well as arrays of chemical species. Preferably, the solvent has the formula (I): wherein A=O or S; X=O, S or N (C1-C4 alkyl) Y=O, S, N(C1-C4 alkyl) or CH2; and R=C1-C20 straight or branched chain alkyl.

Abstract: This invention relates to methods of preventing or reducing the severity of psoriasis. In one embodiment, the method involves administering to the individual a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor, present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells. In particular, the T cell receptor has the V&bgr; region-V&bgr;3, V&bgr;13.1 or V&bgr;17. In another embodiment, the method involves gene therapy. The invention also relates to methods of diagnosing psoriasis by determining the presence of psoriasis predominant T cell receptors.

Abstract: The present invention provides a method for identifying a thermostable polymerase having altered fidelity. The method consists of generating a random population of polymerase mutants by mutating at least one amino acid residue of a thermostable polymerase and screening the population for one or more active polymerase mutants by genetic selection. For example, the invention provides a method for identifying a thermostable polymerase having altered fidelity by mutating at least one amino acid residue in an active site O-helix of a thermostable polymerase. The invention also provides thermostable polymerases and nucleic acids encoding thermostable polymerases having altered fidelity, for example, high fidelity polymerases and low fidelity polymerases. The invention additionally provides a method for identifying one or more mutations in a gene by amplifying the gene with a high fidelity polymerase.

Abstract: The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic moieties adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic. moiety an adjacent positively charged moiety. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.